Methods and systems for endobronchial diagnosis

ABSTRACT

A method of diagnosing an air leak in a lung compartment of a patient may include: advancing a diagnostic catheter into an airway leading to the lung compartment; inflating an occluding member on the catheter to form a seal with a wall of the airway and thus isolate the lung compartment; measuring air pressure within the lung compartment during multiple breaths, using the diagnostic catheter; displaying the measured air pressure as an air pressure value on a console coupled with the diagnostic catheter; and determining whether an air leak is present in the lung compartment based on the displayed air pressure value during the multiple breaths.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/159,670 (Attorney Docket No. 20920-764.401), filed May 19, 2016, nowU.S. patent Ser. No. ______, which is a divisional of U.S. patentapplication Ser. No. 13/174,665 (Attorney Docket No. 20920-764.201),filed Jun. 30, 2011, now U.S. Pat. No. 9,364,168, which claims priorityunder 35 U.S.C. § 119(e) as a non-provisional application of U.S.Provisional Patent Application Ser. No. 61/360,816, entitled Methods andSystems for Endobronchial Diagnosis, filed Jul. 1, 2010, the fulldisclosures of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

This invention relates generally to methods for diagnosis and treatmentof lung disease.

2. Description of the Related Art

Chronic obstructive pulmonary disease (COPD), including emphysema andchronic bronchitis, is a significant medical problem currently affectingaround 16 million people in the U.S. alone (about 6% of the U.S.population). In general, two types of diagnostic tests are performed ona patient to determine the extent and severity of COPD: 1) imagingtests; and 2) functional tests. Imaging tests, such as chest x-rays,computerized tomography (CT) scans, Magnetic Resonance Imaging (MRI)images, perfusion scans, and bronchograms, provide a good indicator ofthe location, homogeneity and progression of the diseased tissue.However, imaging tests do not provide a direct indication of how thedisease is affecting the patient's overall lung function andrespiration. Lung function can be better assessed using functionaltesting, such as spirometry, plethysmography, oxygen saturation, andoxygen consumption stress testing, among others. Together, these imagingand functional diagnostic tests are used to determine the course oftreatment for the patient.

One of the emerging treatments for COPD involves the endoscopicintroduction of endobronchial occluders or endobronchial one-way valvedevices (“endobronchial valves” or “EBVs”) into pulmonary airways tocause atelectasis (i.e., collapse) of a diseased/hyperinflated lungcompartment, thus reducing the volume of that lung portion and allowinghealthier lung compartments more room to breathe and perhaps reducingpressure on the heart. Examples of such a method and implant aredescribed, for example, in U.S. patent application Ser. No. 11/682,986and U.S. Pat. No. 7,798,147, the full disclosures of which are herebyincorporated by reference. One-way valves implanted in airways leadingto a lung compartment restrict air flow in the inhalation direction andallow air to flow out of the lung compartment upon exhalation, thuscausing the adjoining lung compartment to collapse over time. Occludersblock both inhalation and exhalation, also causing lung collapse overtime.

It has been suggested that the use of endobronchial implants for lungvolume reduction might be most effective when applied to lungcompartments which are not affected by collateral ventilation.Collateral ventilation occurs when air passes from one lung compartmentto another through a collateral channel rather than the primary airwaychannels. If collateral airflow channels are present in a lungcompartment, implanting a one-way valve or occluder might not be aseffective, because the compartment might continue to fill with air fromthe collateral source and thus fail to collapse as intended. In manycases, COPD manifests itself in the formation of a large number ofcollateral channels caused by rupture of alveoli due to hyperinflation,or by destruction and weakening of alveolar tissue.

An endobronchial catheter-based diagnostic system typically used forcollateral ventilation measurement is disclosed in U.S. PatentPublication No. 2003/0051733 (hereby incorporated by reference), whereinthe catheter uses an occlusion member to isolate a lung segment and theinstrumentation is used to gather data such as changes in pressure andvolume of inhaled/exhaled air. Current state of the art methods forcollateral ventilation measurement are disclosed in U.S. Pat. No.7,883,471 and U.S. Patent Publication Nos. 2008/0027343 and 2007/0142742(all of which are hereby incorporated by reference), in which anisolation catheter is used to isolate a target lung compartment andpressure changes therein are sensed to detect the extent of collateralventilation. The applications also disclose measurement of gasconcentrations to determine the efficiency of gas exchange within thelung compartment. Similar methods are disclosed in PCT Application No.WO2009135070A1 (hereby incorporated by reference), wherein gasconcentration changes in a catheter-isolated lung portion allowcollateral ventilation to be determined.

In addition to assessing collateral ventilation, there is an unmet needfor quantifiably assessing air leaks (pneumothorax) within the lung. Thelung is surrounded by a pleural cavity that ordinarily maintains apressure that is slightly negative compared to atmospheric pressure.This slight negative pressure helps the lung inhale air from theatmosphere. An air leak occurs when a portion of the lung starts to leakair into the pleural cavity, thus removing the normal, negative pressurein the cavity and often leading to collapse of the lung. Such an airleak is caused by multiple factors such as disease, trauma to the lung,or as a complication of medical treatment.

Traditional methods of measuring air leaks have focused on a purelyqualitative analysis of whether a leak exists rather than quantitativemeasures of the amount of leakage. Furthermore, the existing methodsoften rely on invasive means for diagnosis. For example, a Pleur-Evac®system (available from Teleflex Medical, www.teleflexmedical.com) relieson obtaining air from the pleural cavity via a catheter implanted intothe pleural space via the chest. The air thus obtained from the pleuralcavity is allowed to bubble through a fluid, and the quantity of thebubbles is correlated to the extent of the leak within the cavity. Sucha method is inaccurate for multiple reasons. Since the value is obtainedfrom the pleural cavity as a whole, there is no indication of where theair leak is located. The system also does not indicate the impact of theair leak on important parameters of lung function such as pressure orflow. Finally, the Pleur-Evac® system also does not indicate whetherthere are multiple air leaks and the rate of contribution of each airleak to the whole.

Therefore, a need exists for a more accurate and complete diagnosticmethod for quantifying air leaks within the lung. As discussed above, aneed also exists for improved methods and systems to determine thepresence of collateral channels and/or collateral ventilation. At leastsome of these objectives will be met by the embodiments describedfurther below.

SUMMARY OF THE INVENTION

In one aspect of the present invention, a method of diagnosing an airleak in a lung compartment of a patient may involve: advancing adiagnostic catheter into an airway leading to the lung compartment;inflating an occluding member on the catheter to form a seal with a wallof the airway and thus isolate the lung compartment; measuring airpressure within the lung compartment during multiple breaths, using thediagnostic catheter; displaying the measured air pressure as an airpressure value on a console coupled with the diagnostic catheter; anddetermining whether an air leak is present in the lung compartment basedon the displayed air pressure value during the multiple breaths.

In some embodiments, the console displays multiple air pressure valuesmeasured during the multiple breaths as a wave-form. In one embodiment,the console may display a wave-form displaying a base-line value. In oneembodiment, a negative base-line value may be correlated with a size ofan air leak. In some embodiments, the method may further includedisplaying on the console whether the air leak is present in thecompartment. In some embodiments, the lung compartment may be a lobe ofa lung, while in alternative embodiments the lung compartment may be asegment of a lung.

Optionally, some embodiments of the method may further involve using thediagnostic catheter to assess whether there is collateral ventilationinto the lung compartment and determining a treatment method based onthe determinations of the air leak and collateral ventilation. Someembodiments may further involve measuring air flow out of the lungcompartment during the multiple breaths, using the catheter, anddisplaying the measured air flow as an air flow value. In suchembodiments, the determining step may be based on the air pressure valueand/or the air flow value. Any of the methods may be repeated to assessmultiple lung compartments.

In another aspect of the present invention, a method of diagnosing anair leak in a lung compartment of a patient may include: advancing adiagnostic catheter into an airway leading to the lung compartment;inflating an occluding member on the catheter to form a seal with a wallof the airway and thus isolate the lung compartment; measuring air flowout of the lung compartment during multiple breaths, using thediagnostic catheter; displaying the measured air flow as an air flowvalue on a console coupled with the diagnostic catheter; and determiningwhether an air leak is present in the lung compartment based on thedisplayed air flow value during the multiple breaths.

In one embodiment, the measuring step may involve measuring air flowduring inspiration and expiration. In such an embodiment, thedetermining step may include comparing air flow during inspiration toair flow during expiration. The determining step may optionally alsoinclude calculating a ratio of inspiration air flow to expiration airflow. In some embodiments, the method may further include estimating asize of the air leak based on the ratio. Also optionally, the method mayfurther involve displaying on the console whether an air leak ispresent.

These and other aspects and embodiments of the present invention are setforth in further detail below, in reference to the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention has other advantages and features which will be morereadily apparent from the following detailed description of theinvention and the appended claims, when taken in conjunction with theaccompanying drawings, in which:

FIG. 1 shows a diagnostic or assessment catheter used in methodsaccording to one embodiment of the present invention;

FIG. 2 shows the placement of the catheter shown in FIG. 1 in the lungaccording to one embodiment;

FIG. 3 shows a console configured to receive the catheter shown in FIG.1 according to one embodiment;

FIG. 4 shows a graph indicating an air leak according to one embodiment;and

FIG. 5 shows a graph showing the presence of an air leak.

DETAILED DESCRIPTION OF THE INVENTION

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the invention but merely asillustrating different examples and aspects of the invention. Variousmodifications, changes and variations may be made in the disclosedembodiments without departing from the spirit and scope of theinvention.

The present application provides methods and systems for targeting,accessing and diagnosing diseased lung compartments. Such compartmentsmay be an entire lobe, a segment, a sub-segment or any such portion ofthe lung. In the disclosed embodiments, lung functionality is assessedby isolating a lung compartment to obtain various measurements. ThoughCOPD is mentioned as an example, the applicability of these methods fortreatment and diagnosis is not limited to COPD, but can be applicable toany lung disease.

The methods are minimally invasive in the sense that the requiredinstruments are introduced orally, and the patient is allowed to breathenormally during the procedures. The methods involve detecting thepresence or characteristics (e.g., concentration or pressure) of one ormore naturally occurring or introduced gases to determine the presenceof collateral ventilation, or may involve measurement of oxygensaturation of tissue.

In some embodiments, isolation of the lung comprises sealingly engaginga distal end of a catheter in an airway feeding a lung compartment, asshown in FIGS. 1 and 2. Such a catheter has been disclosed in co-pendingpublished U.S. patent application Ser. No. 10/241,733, which isincorporated herein by reference. As shown in FIG. 1, the catheter 100comprises a catheter body 110, and an expandable occluding member 120 onthe catheter body. The catheter body 110 has a distal end 102, aproximal end 101, and at least one lumen 130, extending from a locationat or near the distal end to a location at or near the proximal end.

The proximal end of catheter 100 is configured to be coupled with anexternal control unit (or “console,” not shown), and optionallycomprises an inflation port (not shown). The distal end of catheter 100is adapted to be advanced through a body passageway such as a lungairway. The expandable occluding member 120 is disposed near the distalend of the catheter body and is adapted to be expanded in the airwaywhich feeds the target lung compartment. In one embodiment, theoccluding member 120 is a compliant balloon made of transparentmaterial. The transparent material allows visualization using thebronchoscope through the balloon. The occluding member 120 is inflatablevia a syringe that is configured to be coupled to the inflation port.Optionally, catheter 100 comprises visual markers at the proximal anddistal ends of the balloon to identify the location of the occludingmember 120 within the airway prior to inflation. The occluding member120 material inflates and seals with inflation pressures between 5-20psi to prevent balloon migration within the airway. This inflationpressure also aids the occluding member 120 in maintaining a symmetricalconfiguration within the airway, thereby ensuring that the catheter(which is centered within the occluding member 120) will remain centeredwithin the airway. The occluding member 120 material and attachment arealso configured to minimize longitudinal movement of the occludingmember 120 relative to the catheter body 110 itself. To accommodate thehigher inflation pressure, the occluding member 120 is made of apolyurethane such as Pellethane 80A, but can be made of any materialthat is configured to maintain structural integrity at a high inflationpressure.

Additionally and optionally, catheter 100 may further comprise at leastone gas sensor 140 located within or in-line with the lumen 130 forsensing characteristics of various gases in air communicated to and fromthe lung compartment. The sensors may comprise any suitable sensors orany combination of suitable sensors, and are configured to communicatewith control unit 200. Some embodiments of sensors include pressuresensors, temperature sensors, air flow sensors, gas-specific sensors, orother types of sensors. As shown in FIG. 1, the sensors 140 may belocated near the distal end 102 of the catheter 100. Alternatively, thesensors 140 may be located at any one or more points along the catheter100, or in-line with the catheter 100 and within the control unit withone or more measuring components.

As shown in FIG. 2, at least a distal portion of the catheter body 110is adapted to be advanced into and through the trachea (T). The cathetermay optionally be introduced through or over an introducing device suchas a bronchoscope. The distal end 102 of the catheter body 110 can thenbe directed to a lung lobe (LL) to reach an airway (AW) which feeds atarget lung compartment (TLC), which is to be assessed. When theoccluding member 120 is expanded in the airway, the correspondingcompartment is isolated with access to and from the compartment providedthrough the lumen 130.

Referring now to FIG. 3, the proximal end of the catheter 100 may beconfigured to be coupled with a control unit (or “console”) 200. Thecontrol unit 200 comprises one or more measuring components (not shown)to measure lung functionality. The measuring components may take manyforms and may perform a variety of functions. For example, thecomponents may include a pulmonary mechanics unit, a physiologicaltesting unit, a gas dilution unit, an imaging unit, a mapping unit, atreatment unit, a pulse oximetry unit or any other suitable unit. Thecomponents may be disposed within the control unit 200, or may beattached to the unit 200 from an external source. The control unit 200comprises an interface for receiving input from a user and a displayscreen 210. The display-screen 210 will optionally be a touch-sensitivescreen, and may display preset values. Optionally, the user will inputinformation into the control unit 200 via a touch-sensitive screenmechanism. Additionally and optionally, the control unit 200 may beassociated with external display devices such as printers or chartrecorders. At least some of the above system embodiments will beutilized in the methods described below.

Assessment of Pleural Air Leak in Patients. One diagnostic test that canbe undertaken using the above system is the measurement of air leaksfrom the lung into the pleural cavity. In order to do this, the catheteris introduced into a lung compartment, as shown in FIG. 2, and thepressure is measured. An unusually negative pressure indicates thepresence of an air leak.

To begin, catheter 100 is placed into an airway leading to a target lungcompartment (TLC) and the occluding member 120 is inflated to isolatethe TLC. Thereafter, negative pressure within the TLC is monitored. Ifthe negative pressure becomes increasingly negative over time, this mayindicate that there is a leak into the pleural cavity from another lungcompartment. If a strong and consistent negative pressure is observed,this indicates an air leak within the TLC being tested.

FIGS. 4 and 5 show exemplary graphs of the above as they would bedisplayed on the console 200 during a test. In FIG. 4, after occlusionby the occluding member, it is apparent that negative pressure readingsare recorded. This in itself is normal, as during regular breathingnegative pressure builds during inhalation and reduces duringexhalation. Negative pressure during inhalation would thus be expectedin a normal lung compartment. However, as apparent in FIG. 4, there is atrend towards greater negative pressure within the compartment overtime. This indicates that there may be another source of negativepressure within the lung, for example in an adjacent lung lobe orsegment. FIG. 4 thus is a representative graph of a suspected air leakin an adjoining lung compartment. If encountered, a user would study oneor more adjacent compartments for the presence of an air leak.

In contrast, FIG. 5 is an example of a pressure graph showing theresulting wave-form from a lung compartment in which an air leak ispresent. As apparent in the graph, after isolation, the pressure becomesnegative relatively quickly and maintains a very low negative baselineduring the course of the test when the compartment remains isolated.Respiration is still being recorded, as there are still inflections inthe wave-form (denoted by the arrow ‘A’) as inhalation occurs. Thisphenomenon occurs because the leak allows the pressure within thecompartment to normalize with the natural negative pressure of thepleural cavity.

Once an air leak has thus been identified, it is easily quantified byreferring to the baseline value of the negative pressure. A smaller airleak creates less negative pressure and thus displays a greater baselinevalue than a larger air leak.

Additionally or alternatively, flow may be monitored to determine thepresence and extent of an air leak. If a normal lung is isolated suchthat only exhalation is recorded through the catheter, positive flowincreases during exhalation and is reduced to zero during inhalation. Ifan air leak exists, during flow monitoring, the graphs on the consoledisplay a sudden increase in flow, followed by a gradual drop. If bothinspiratory and expiratory flows are followed, wherever the leak exists,a higher ratio of inspiratory to expiratory flow is expected than wouldbe seen in a normal lung compartment. This is due to the fact thatduring inspiration, greater flow exists as the pressure within thepleural space draws more air from the compartment. Furthermore, themagnitude of the flow ratio indicates the magnitude of the leak, with agreater ratio correlating to a more sizable leak.

Optionally, external sources may also be used to facilitate the testing.For example, the patient may be placed on a ventilator to ensureregulated airflow into the lung. Further, rather than using the console200 at the proximal end of catheter 100, a manometer or a flow gauge maybe used to determine flow rate. Further, the catheter 100, with orwithout console 200, may be used in conjunction with commercial systemssuch as the Pleur-Evac® system to improve the performance of thosesystems. For example, the catheter may be used to infuse a gas marker orcolored gas into the lung compartment to allow for easy viewing in thePleur-Evac® system. Further, the catheter may be used to speed healingby applying suction pressure to the affected lung compartment in thehopes of closing the air leak.

Once a diagnosis of an air leak has been made, a treatment plan may bedetermined. Since the size of the air leak is correlated with the timefor the air leak to heal, information on the size of the air leak couldbe used to predict the length of time necessary for healing. Further,the region subject to the air leak may be sealed off from the rest ofthe lung using endobronchial valves or any other method. This wouldensure that the surrounding lung compartments are not affected by thepressure differential caused by the air leak, while simultaneouslyallowing the air leak to heal over time.

Additionally, the diagnosis of an air leak may be combined with otherdiagnoses in order to more effectively treat the patient. For example,an air leak diagnosis may be combined with a diagnosis of collateralventilation in order to determine a more accurate method of treatment.This is particularly useful because if a lung compartment with an airleak is subject to collateral ventilation, treatment by sealing thecompartment alone would be insufficient, as air would escape throughcollateral channels into neighboring compartments. Thus, a diagnosis ofcollateral ventilation in conjunction with a diagnosis of air leak wouldallow identification of all the compartments that would need to besealed in order to effectively contain the air leak. In someembodiments, the same methods described above for measuring pressureand/or flow within a lung compartment may be used to assess collateralventilation in a compartment.

Although certain embodiments of the disclosure have been described indetail, certain variations and modifications will be apparent to thoseskilled in the art, including embodiments that do not provide all thefeatures and benefits described herein. It will be understood by thoseskilled in the art that the present disclosure extends beyond thespecifically disclosed embodiments to other alternative or additionalembodiments and/or uses and obvious modifications and equivalentsthereof. In addition, while a number of variations have been shown anddescribed in varying detail, other modifications, which are within thescope of the present disclosure, will be readily apparent to those ofskill in the art based upon this disclosure. It is also contemplatedthat various combinations or sub-combinations of the specific featuresand aspects of the embodiments may be made and still fall within thescope of the present disclosure. Accordingly, it should be understoodthat various features and aspects of the disclosed embodiments can becombined with or substituted for one another in order to form varyingmodes of the present disclosure. Thus, it is intended that the scope ofthe present disclosure herein disclosed should not be limited by theparticular disclosed embodiments described above. For all of theembodiments described above, the steps of any methods need not beperformed sequentially.

1. (canceled)
 2. A method of diagnosing an air leak in a lungcompartment of a patient, the method comprising: advancing a diagnosticcatheter into an airway leading to the lung compartment; inflating anoccluding member on the catheter to form a seal with a wall of theairway and thus isolate the lung compartment; measuring air pressurewithin the isolated lung compartment during multiple breaths, using thediagnostic catheter; displaying the measured air pressure as an airpressure value on a console coupled with the diagnostic catheter; anddetermining whether an air leak is present in the lung compartment basedon the displayed air pressure value during the multiple breaths.
 3. Themethod of claim 2, further comprising externally applying suctionpressure to the pleural cavity; wherein the measured air pressure isnegative and is based on the external suction pressure being applied tothe pleural cavity; and determining that an air leak is present in thelung compartment.
 4. The method of claim 2, further comprisingexternally applying suction pressure to the pleural cavity; wherein themeasured air pressure is negative and then maintains a negative baselinevalue during multiple breaths; and is based on the external suctionpressure being applied to the pleural cavity; and determining that anair leak is present in the lung compartment.
 5. The method of claim 3,wherein a magnitude of the negative air pressure is correlated with asize of the air leak.
 6. The method of claim 2, further comprisingexternally applying suction pressure to the pleural cavity; wherein themeasured air pressure does not maintain a negative baseline value duringmultiple breaths thus indicating that the lung compartment beingmeasured is not communicating to the external suction pressure beingapplied to the pleural cavity; and determining that an air leak is notpresent in the lung compartment.
 7. The method of claim 2, furthercomprising repeating the steps to assess at least one additional lungcompartment.
 8. The method of claim 3, further comprising repeating thesteps to assess at least one additional lung compartment.
 9. The methodof claim 4, further comprising repeating the steps to assess at leastone additional lung compartment.
 10. The method of claim 6, furthercomprising repeating the steps to assess at least one additional lungcompartment.
 11. The method of claim 2, wherein the console displaysmultiple air pressure values measured as a wave-form.
 12. The method ofclaim 3, wherein the console displays multiple air pressure valuesmeasured as a wave-form.
 13. The method of claim 4, wherein the consoledisplays multiple air pressure values measured as a wave-form.
 14. Themethod of claim 6, wherein the console displays multiple air pressurevalues measured as a wave-form.
 15. The method of claim 2, furthercomprising displaying on the console whether the air leak is present inthe compartment.
 16. The method of claim 2, wherein the lung compartmentcomprises a lobe of a lung.
 17. The method of claim 2, wherein the lungcompartment comprises a segment of a lung.
 18. The method of claim 2,further comprising: using the diagnostic catheter to assess whetherthere is collateral ventilation into the lung compartment; anddetermining a treatment method based on the determinations of the airleak and collateral ventilation.